The overall objective of this work is to understand how dehydrogenases function. In particular, we plan to examine three aspects of the structure and function of glyceraldehyde-3-phosphate dehydrogenase: a. cooperativity and non-cooperativity in coenzyme binding with several forms of the enzyme, b. the interaction of inorganic phosphate with the enzyme, and c. the effect of naturally occurring inhibitors on the structure and function of the enzyme. These studies are aimed at obtaining a better understanding of the relation between structure and function of an important enzyme in the metabolism of all cells, glyceraldehyde-3-phosphate dehydrogenase. More generally, the studies of coenzyme binding to this enzyme should contribute substantially to the understanding of the phenomenon of negative cooperativity in ligand binding and half-of-sites reactivity of enzymes with multiple subunits.